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Unintended effects of cardiovascular drugs on the pathogenesis of Alzheimer's disease.

Wang J, Zhao Z, Lin E, Zhao W, Qian X, Freire D, Bilski AE, Cheng A, Vempati P, Ho L, Ono K, Yamada M, Pasinetti GM - PLoS ONE (2013)

Bottom Line: Among these medications, some might benefit, while others might exacerbate, the pathogenesis of AD.Our study suggests that some commonly prescribed drugs might exert unintended effects and modulate AD and provides the basis for continuing investigation of the role of individual drugs on a case-by-case basis.This line of investigation will lead to the identification of common medications that are potentially beneficial or detrimental to AD as a reference for physicians to consider when prescribing the most appropriate drugs for their patients, particularly for treating chronic disorders among the growing geriatric population.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, New York, United States of America.

ABSTRACT
Alzheimer's disease (AD) is rapidly becoming one of the leading causes of disability and mortality in the elderly. As life-expectancy increases, an increasing number of people will rely on modern medicines to treat age-associated disorders. Among these medications, some might benefit, while others might exacerbate, the pathogenesis of AD. We screened 1,600 FDA approved drugs for β-amyloid (Aβ)-modifying activity and identified drugs that can potentially influence amyloid precursor protein processing. In this study, we focused on cardiovascular drugs and demonstrated that some hypertensive medication can differentially modulate Aβ, both in vitro and in vivo. Our study suggests that some commonly prescribed drugs might exert unintended effects and modulate AD and provides the basis for continuing investigation of the role of individual drugs on a case-by-case basis. This line of investigation will lead to the identification of common medications that are potentially beneficial or detrimental to AD as a reference for physicians to consider when prescribing the most appropriate drugs for their patients, particularly for treating chronic disorders among the growing geriatric population.

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Related in: MedlinePlus

Schematic diagram of primary screening of 1600 FDA approved drugs.
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Related In: Results  -  Collection


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pone-0065232-g001: Schematic diagram of primary screening of 1600 FDA approved drugs.

Mentions: Our high throughput screening study assessed 1600 FDA approved drugs for their ability to modulate Aβ activity. We found 559 drugs of the 1600 had no effect on APP processing or were toxic to neurons at the testing concentration, while 800 drugs could reduce Aβ content over 10% in primary neurons derived from Tg2576 mice, among which, 184 drugs were able to reduce Aβ content greater than 30% compared to vehicle. We also found 241 drugs could potentially promote Aβ accumulation including 26 drugs that could increase the level of Aβ greater than 30% compared to vehicle treatment (Figure 1).


Unintended effects of cardiovascular drugs on the pathogenesis of Alzheimer's disease.

Wang J, Zhao Z, Lin E, Zhao W, Qian X, Freire D, Bilski AE, Cheng A, Vempati P, Ho L, Ono K, Yamada M, Pasinetti GM - PLoS ONE (2013)

Schematic diagram of primary screening of 1600 FDA approved drugs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675203&req=5

pone-0065232-g001: Schematic diagram of primary screening of 1600 FDA approved drugs.
Mentions: Our high throughput screening study assessed 1600 FDA approved drugs for their ability to modulate Aβ activity. We found 559 drugs of the 1600 had no effect on APP processing or were toxic to neurons at the testing concentration, while 800 drugs could reduce Aβ content over 10% in primary neurons derived from Tg2576 mice, among which, 184 drugs were able to reduce Aβ content greater than 30% compared to vehicle. We also found 241 drugs could potentially promote Aβ accumulation including 26 drugs that could increase the level of Aβ greater than 30% compared to vehicle treatment (Figure 1).

Bottom Line: Among these medications, some might benefit, while others might exacerbate, the pathogenesis of AD.Our study suggests that some commonly prescribed drugs might exert unintended effects and modulate AD and provides the basis for continuing investigation of the role of individual drugs on a case-by-case basis.This line of investigation will lead to the identification of common medications that are potentially beneficial or detrimental to AD as a reference for physicians to consider when prescribing the most appropriate drugs for their patients, particularly for treating chronic disorders among the growing geriatric population.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, New York, United States of America.

ABSTRACT
Alzheimer's disease (AD) is rapidly becoming one of the leading causes of disability and mortality in the elderly. As life-expectancy increases, an increasing number of people will rely on modern medicines to treat age-associated disorders. Among these medications, some might benefit, while others might exacerbate, the pathogenesis of AD. We screened 1,600 FDA approved drugs for β-amyloid (Aβ)-modifying activity and identified drugs that can potentially influence amyloid precursor protein processing. In this study, we focused on cardiovascular drugs and demonstrated that some hypertensive medication can differentially modulate Aβ, both in vitro and in vivo. Our study suggests that some commonly prescribed drugs might exert unintended effects and modulate AD and provides the basis for continuing investigation of the role of individual drugs on a case-by-case basis. This line of investigation will lead to the identification of common medications that are potentially beneficial or detrimental to AD as a reference for physicians to consider when prescribing the most appropriate drugs for their patients, particularly for treating chronic disorders among the growing geriatric population.

Show MeSH
Related in: MedlinePlus